Saccade behaviour in migraine patients

Background: Voxel-based morphometry studies in migraine patients showed significant grey matter volume reduction in regions involved in the control of saccadic eye movements. We hypothesized that these changes would be reflected in dysfunctional saccadic behaviour. Methods: Saccades were recorded by infrared oculography using three different paradigms (pro-saccade with gap, prosaccade overlap and anti-saccade with gap). We compared the results for migraine patients (n = 80) with those for controls (n = 87). Results: No significant differences were found between migraine patients with (n = 46) and without (n = 34) aura. Migraine patients showed a saccadic behaviour that differed from controls in three respects. In migraine patients, the latencies in the pro-saccade with gap paradigm were borderline significantly longer. Moreover, in both the pro-saccade with gap and the pro-saccade overlap paradigm we observed a larger intra-individual variation of the latency in migraine patients. However, the biggest difference was that the patients who received migraine prophylactic therapy made significantly more anti-saccade errors in the anti-saccade with gap paradigm, suggesting that inhibitory saccade control is impaired in migraine patients depending on the severity of the migraine. Conclusion: We suggest a deficient inhibitory control, reflecting an executive dysfunction in the dorsolateral prefrontal cortex or a dysfunction in the cingulate cortex, is present in migraine patients

Deciphering the morphology of motor evoked potentials

Motor Evoked Potentials (MEPs) are used to monitor disability progression in multiple sclerosis (MS). Their morphology plays an important role in this process. Currently, however, there is no clear definition of what constitutes a normal or abnormal morphology. To address this, five experts independently labeled the morphology (normal or abnormal) of the same set of 1,000 MEPs. The intra- and inter-rater agreement between the experts indicates they agree on the concept of morphology, but differ in their choice of threshold between normal and abnormal morphology. We subsequently performed an automated extraction of 5,943 time series features from the MEPs to identify a valid proxy for morphology, based on the provided labels. To do this, we compared the cross-validation performances of one-dimensional logistic regression models fitted to each of the features individually. We find that the approximate entropy (ApEn) feature can accurately reproduce the majority-vote labels. The performance of this feature is evaluated on an independent test set by comparing to the majority vote of the neurologists, obtaining an AUC score of 0.92. The model slightly outperforms the average neurologist at reproducing the neurologists consensus-vote labels. We can conclude that MEP morphology can be consistently defined by pooling the interpretations from multiple neurologists and that ApEn is a valid continuous score for this. Having an objective and reproducible MEP morphological abnormality score will allow researchers to include this feature in their models, without manual annotation becoming a bottleneck. This is crucial for large-scale, multi-center datasets. An exploratory analysis on a large single-center dataset shows that ApEn is potentially clinically useful. Introducing an automated, objective, and reproducible definition of morphology could help overcome some of the barriers that are currently obstructing broad adoption of evoked potentials in daily care and patient follow-up, such as standardization of measurements between different centers, and formulating guidelines for clinical use

Two Time Point MS Lesion Segmentation in Brain MRI:An Expectation-Maximization Framework

Purpose: Lesion volume is a meaningful measure in multiple sclerosis (MS) prognosis. Manual lesion segmentation for computing volume in a single or multiple time points is time consuming and suffers from intra and inter-observer variability. Methods: In this paper, we present MSmetrix-long: a joint expectation-maximization (EM) framework for two time point white matter (WM) lesion segmentation. MSmetrix-long takes as input a 3D T1-weighted and a 3D FLAIR MR image and segments lesions in three steps: (1) cross-sectional lesion segmentation of the two time points; (2) creation of difference image, which is used to model the lesion evolution; (3) a joint EM lesion segmentation framework that uses output of step (1) and step (2) to provide the final lesion segmentation. The accuracy (Dice score) and reproducibility (absolute lesion volume difference) of MSmetrix-long is evaluated using two datasets. Results: On the first dataset, the median Dice score between MSmetrix-long and expert lesion segmentation was 0.63 and the Pearson correlation coefficient (PCC) was equal to 0.96. On the second dataset, the median absolute volume difference was 0.11 ml. Conclusions: MSmetrix-long is accurate and consistent in segmenting MS lesions. Also, MSmetrix-long compares favorably with the publicly available longitudinal MS lesion segmentation algorithm of Lesion Segmentation Toolbox

Fluoxetine in Progressive Multiple Sclerosis (FLUOX-PMS) : study protocol for a randomized controlled trial

Background: Currently available disease-modifying treatments acting by modifying the immune response are ineffective in progressive multiple sclerosis (MS), which is caused by a widespread axonal degeneration. Mechanisms suspected to be involved in this widespread axonal degeneration are reduced axonal energy metabolism, axonal glutamate toxicity, and reduced cerebral blood flow. Fluoxetine might theoretically reduce axonal degeneration in MS because it stimulates energy metabolism through enhancing glycogenolysis, stimulates the production of brain-derived neurotrophic factor, and dilates cerebral arterioles. The current document presents the protocol of a clinical trial to test the hypothesis that fluoxetine slows down the progressive phase of MS. Methods/Design: The FLUOX-PMS trial is a multi-center, randomized, controlled and double-blind clinical study. A total of 120 patients with the diagnosis of either secondary or primary progressive MS will be treated either by fluoxetine (40 mg daily) or placebo for a total period of 108 weeks. The primary endpoint is the time to confirmed disease progression defined as either at least a 20% increase in the timed 25-Foot Walk or at least a 20% increase in the 9-Hole Peg Test. Secondary endpoints include the Hauser ambulation index, cognitive changes, fatigue, magnetic resonance imaging of the brain, and in a small subgroup optical coherence tomography. Discussion: The FLUOX-PMS trial will gives us information as to whether fluoxetine has neuroprotective effects in patients with progressive MS

Cerebral oedema in episodic ataxia

We report a patient with episodic ataxia (presumably of type 2) who developed cerebral oedema secondary to a common infection (presumably viral). Cerebral oedema may be a part of the clinical spectrum of familial episodic ataxia and argues for an overlap with hemiplegic migraine. It is suggested to consider a diagnosis of episodic ataxia or familial hemiplegic migraine in catastrophic reactions to apparent trivial trauma or injection

Apraclonidine and my pupil

Purpose Used in the diagnosis of Horner's syndrome, apraclonidine 1% dilatates the involved eye due to denervation supersensitivity. Recent literature suggests that in healthy volunteers, apraclonidine provokes a mild miotic effect. Since the comparison of both the pathologic and the non-pathologic eye is important, we wanted to further investigate the effect of apraclonidine on the healthy eye. By measuring the effect on the pupil intermittently over a few hours, we tried to determine the best moment for evaluation after instillation with apraclonidine. Therefore, the effect of apraclonidine on pupillary parameters was investigated in 14 healthy volunteers. Methods Infrared pupillography was used to measure the scotopic pupil diameter and the dynamic pupil responses to light. The first measurements were performed prior to instillation of apraclonidine. Measurements were retaken 30, 60, 90, 120, 180, 240, 300 and 360 min after random instillation of one eye with one drop of 1% apraclonidine. Results The anisocoria after dark adaptation and at minimum pupil diameter differed significantly for the measurements obtained 30 and 60 min after instillation with apraclonidine. The eye with apraclonidine drops showed relative miosis and an increased amplitude of constriction to light. No significant influence was found on the latency, the constriction velocity and redilation velocity. Conclusions Instillation of apraclonidine 1% in healthy subjects causes relative miosis, which is most pronounced after 30-60 min. The amplitude of constriction to light also differs significantly. The relative miotic effect of apraclonidine could be explained by the alpha-2 receptor agonistic effect which is more pronounced than the alpha-1 agonistic effect in healthy subjects. In patients with Horner's syndrome, the alpha-1 agonistic effect will dominate because of the supersensitivity of the alpha-1 receptors, resulting in relative mydriasis. These findings stress the necessity to instill the unaffected eye in diagnosing a suspected Horner's pupil

Episodische ataxie

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Niet-diabetische lumbosacrale radiculoplexusneuropathie

Non-diabetic lumbosacral radiculoplexus neuropathy Non-diabetic lumbosacral radiculoplexus neuropathy is an idiopathic plexopathy with a low incidence. Patients present with unilateral or asymmetric aching pain of abrupt to subacute onset, located in the leg. Progressive loss of strength occurs, possibly associated with sensory complaints. The non-diabetic form is less frequent than the diabetic one. Diagnosis is based on clinical signs and neurophysiological investigations. Besides diabetes, infiltrative and compressive processes have to be excluded. Traumatic forms are evident. An autoimmune mediated mechanism is presumed. Besides control of the neuropathic pain, treatment consists of immune mediating medication. This pathology is illustrated in the manuscript by the clinical history of a 64-year-old not diabetic man